Impotence is the inability to obtain and sustain an erection sufficient for intercourse. Erection is achieved as a result of arterial inflow into the corpus cavernosum of the penis, which produces engorgement of the corpus cavernosum, and subsequent penile erection. According to a 1993 National Institutes of Health Consensus Panel, it is estimated that as many as 30 million American men experience some degree of erectile dysfunction, the prevalence of which increases with age (NIH Consensus Statement, Vol 10(4): 1-31, (1992)). Fifteen to twenty-five percent of all men 65 years and older suffer from some sort of erectile dysfunction, but the disease is also experienced by as many as five percent of men age 40 years. Half of diabetic men exhibit erectile dysfunction. An increased prevalence of the disease is also associated with hypogonadism, hypertension, high blood cholesterol, drugs, neurogenic disorders, Peyronie's disease, priapism, depression, and renal failure (NIH Consensus Statement, Vol 10(4):1-31, (1992)).
Erectile dysfunction affects men of all races and socioeconomic backgrounds, but little is known concerning its prevalence according to membership in these groups. Reports indicate that the disease is experienced throughout the world.
The causes of impotence are usually divided into two subcategories a) organic and b) psychological. The organic aspects of impotence are caused by underlying vascular disease such as that associated with hypertension, diabetes mellitus, and prescription medications. Conservative estimates indicate that half of all cases of impotence are of vascular origin. Because the physiologic process of erection is initiated by an increase in blood flow through the penile arteries and shunting of blood into the vascular spaces of the corpus cavernosum, erectile dysfunction can result from vasculogenic disorders. Since erection necessarily involves vasodilation of the arteries of the penis, the pathophysiologic basis of impotence can be contributed to the inability of the arteries of the penis to vasodilate, thereby inhibiting the flow of blood into the erectile tissue.
Agents which produce vasodilation either by directly causing vasodilation or indirectly affecting secondary pathways that produce vasodilation have been described, and are currently being used for the treatment of impotence. Among those agents there are included papaverine (J. Urol. 136: 158-161, 1986), phentolamine (J. Urol. 141: 54-57, 1989), prostaglandin E1 (J. Urol. 140: 66-68, 1988; Br. J. Clin. Pharm. 38: 567-571, 1989; J. Urol. 141: 549-550, 1989), linsidomine chlorhydrate (J. Urol. 148: 1437-1440, 1992), yohimbine (J. Urol. 137: 1168-1172, 1987), and trazodone (J. Urol. 145: 60-64, 1991), which have all been used to produce erection in impotent men.
However, these agents induce erection through a vasodilatory mechanism and often exhibit unwanted side-effects. One of the more common side-effects associated with the use of vasodilators for the induction of erection is priapism, a painful erection of exceeding long duration which may result in fibrosis of cavernosal sinusoidal tissue. Examples of specific vasodilating agents causing priapism or extremely long erections following treatment for erectile dysfunction include papaverine (J. Urol. 136: 109, 1986), phentolamine (Br. J. Pharmacol. 87: 495-500, 1987), phenoxybenzamine (Br. J. Pharmacol. 87: 495-500, 1987), and trazodone (J. Urol. 145: 60-64, 1991).
Thus, there is a still a need for an improved treatment of impotence which does not subject an impotent male to the side-effects of known treatments such as the pain associated with erections of extremely long duration and priapism.
Accordingly, it is a primary object of the present invention to provide a method of treating impotence which avoids any undue side effects such as erections of extremely long duration, and the unwanted side-effects such as pain and need for reversal using other agents.
It is another object of the present invention to provide pharmaceutical compositions comprising piperoxan which compositions are effective for the treatment of human male erectile impotence.
It is another object of the present invention to provide a method of treating impotence using piperoxan.
It is yet another object of the present invention to provide pharmaceutical compositions which are safe, effective, and easy to formulate.
Other features and advantages of the present invention will be apparent to those of skill in the art from the following detailed description and appended claims.